The signals and growth factors required for the development of T cells are largely unknown. During early fetal thymus ontogeny, a variety of cell surface molecules are expressed which could potentially serve as transducers of activation signals. Two of such molecules (i.e., Thy-1, and the epsilon-component of the T3 complex) were explored and shown to function in early fetal thymocyte activation, as evidenced by both induction of proliferation and elaboration of lymphokines. We found that both IL-2 and BSF-1/IL-4 are produced upon activation of fetal thymocytes through Thy-1- and T3-activation, and are currently exploring, in an in vitro organ culture system, the effect of blocking IL-2 or IL-4 usage on T cell development. These, as well as other lymphokines currently investigated, could play a role not only as growth factors, but, as preliminary studies indicated, also as differentiation factors. It was demonstrated furthermore, that in the early fetal thymus, all T3-expressing cells are of the gamma-delta phenotype. The significance of this project lies in: (1) understanding the factors that control the development of T cells, and (2) application of this knowledge to studies on immune reconstitution.